title: Enhancer of Zeste homolog 2 (EZH2) is overexpressed in recurrent nasopharyngeal carcinoma and is regulated by miR-26a, miR-101, and miR-98.
abstract: There is increasing evidence supporting the role of members of the polycomb group (PcG) gene family in tumor development and progression. However, their precise role in tumorigenesis and mechanisms of their regulation remain to be elucidated. Using nasopharyngeal carcinoma (NPC) as a disease model, a comprehensive analysis was undertaken on the clinical significance of EZH2 expression, identification of the cellular processes regulated by EZH2, and the mechanisms of its deregulated expression. Herein, we report EZH2 as being associated with a higher risk of relapse in NPC patients (P = 0.002). Genome-wide microarray and bioinformatics identified several vital cellular processes (such as differentiation, development, and apoptosis) to be regulated by EZH2, corroborated by in vitro lethality, and delayed tumor formation in vivo upon EZH2 depletion. The combination of global microRNA (miR) profiling in primary NPC specimens, and in silico analyses provided several candidate miRs that could regulate EZH2. Using a luciferase-based assay, miR-26a, miR-101, and miR-98 were validated as bona fide regulators of EZH2 expression. In particular, miR-98 was underexpressed in relapsed patient samples, strongly suggesting an important role for the miR-98 and EZH2 axis in NPC biology.
authors.affiliation: Division of Applied Molecular Oncology, Ontario Cancer Institute, Toronto, Canada.
authors.forename: N M
authors.initials: NM
authors.lastname: Alajez
authors.forename: W
authors.initials: W
authors.lastname: Shi
authors.forename: A B Y
authors.initials: AB
authors.lastname: Hui
authors.forename: J
authors.initials: J
authors.lastname: Bruce
authors.forename: M
authors.initials: M
authors.lastname: Lenarduzzi
authors.forename: E
authors.initials: E
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Yue
authors.forename: B
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: F-F
authors.initials: FF
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D000071221:Enhancer of Zeste Homolog 2 Protein; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2; D014157:Transcription Factors; C534072:MIRN101 microRNA, human; C528163:MIRN26 microRNA, human; C546084:MIRN98 microRNA, human; C498409:EZH2 protein, human